Journal
CELL REPORTS
Volume 39, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110656
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Funding
- National Natural Science Foundation of China [31900826, 31771258, 32171108]
- Department of Science & Technology of Liaoning Province [2019JH2/10300020]
- Innovation Team Project from the Educational Department of Liaoning Province [LT2016004]
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This study identifies a long non-coding RNA called SNHG12 that plays a crucial role in maintaining the integrity of the blood-brain barrier by directly interacting with TJ protein occludin. The interaction between SNHG12 and occludin is oxygen adaptive and prevents the degradation of occludin, leading to BBB disruption in response to hypoxia. The findings highlight the importance of SNHG12 in maintaining the integrity of the BBB.
Tight junctions (TJs) of brain microvascular endothelial cells (BMECs) play a pivotal role in maintaining the blood-brain barrier (BBB) integrity; however, precise regulation of TJs stability in response to physiological and pathological stimuli remains elusive. Here, using RNA immunoprecipitation with next-generation sequencing (RIP-seq) and functional characterization, we identify SNHG12, a long non-coding RNA (lncRNA), as being critical for maintaining the BBB integrity by directly interacting with TJ protein occludin. The interaction between SNHG12 and occludin is oxygen adaptive and could block Itch (an E3 ubiquitin ligase)-mediated ubiquitination and degradation of occludin in human BMECs. Genetic ablation of endothelial Snhg12 in mice results in occludin reduction and BBB leakage and significantly aggravates hypoxia-induced BBB disruption. The detrimental effects of hypoxia on BBB could be alleviated by exogenous SNHG12 overexpression in brain endothelium. Together, we identify a direct TJ modulator lncRNA SNHG12 that is critical for the BBB integrity maintenance and oxygen adaption.
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